Abstract

Background

Progestational agents may reduce the risk of preterm birth in women with various risk
factors. We sought to test the hypothesis that a weekly dose of 17-hydroxyprogesterone
caproate (17P) given to women with preterm rupture of the membranes (PROM) will prolong
pregnancy and thereby reduce neonatal morbidity.

Methods

Double-blind, placebo-controlled randomized clinical trial. Women with PROM at 23.0
to 31.9 weeks of gestation were randomly assigned to receive a weekly intramuscular
injection of 17P (250 mg in 1 mL castor oil) or placebo (1 mL castor oil). The primary
outcome was the rate of continuing the pregnancy until 34.0 weeks of gestation or
until documentation of fetal lung maturity at 32.0 to 33.9 weeks of gestation. Planned
secondary outcomes were duration of latency period and rate of composite neonatal
morbidity. Enrollment of 111 participants per group, 222 total, was planned to yield
80% power to detect an increase in the primary outcome from 30% with placebo to 50%
with 17P.

Results

Twelve women were enrolled of whom 4 were randomly assigned to receive 17P and 8 to
receive placebo. The trial was terminated prematurely because of two separate issues
related to the supply of 17P. No adverse events attributable to 17P were identified.

Conclusion

Because of premature termination, the trial does not have adequate statistical power
to evaluate efficacy or safety of 17P in women with PROM. Nonetheless, ethical principles
dictate that we report the results, which may contribute to possible future metaanalyses
and systematic reviews.